ALLEVIATION OF THE TEMPERATURE-SENSITIVE PARALYTIC PHENOTYPE OF SHIBIRE(TS) MUTANTS IN DROSOPHILA BY SUB-ANESTHETIC CONCENTRATIONS OF CARBON-DIOXIDE

Cellular mechanisms involved in general anesthesia are unknown. We rep ort here that sub-anesthetic concentrations of carbon dioxide specific ally suppress the temperature-sensitive paralytic phenotype of Drosoph ila shibire(ts) mutants that have a conditional block in synaptic vesi cle recycling. Carbon dioxide not only suppresses the onset of tempera ture-sensitive paralysis, but also rapidly reverses paralysis induced at the restrictive temperature. This effect of CO2 is most pronounced at about 35% in air, and depends on the absolute concentration of avai lable carbon dioxide rather than on the ratio of oxygen to CO2. Other general anesthetics, halothane, N-2 or argon do not suppress the paral ytic phenotype of shibire significantly at concentrations we tested. P aralysis of the other temperature sensitive paralytic mutants in our c ollection is not suppressed by carbon dioxide. These behavioral observ ations are discussed in the light of possible mechanisms underlying pa ralysis of shi(ts) flies. We suggest that spontaneous seizures induced in shi(ts) flies held at their restrictive temperatures cause vesicle depletion at critical synapses and consequent behavioral paralysis. T he effect of subanesthetic concentrations of CO2 may be to depress spo ntaneous CNS activity, thus raising the threshold temperature at which synaptic vesicle depletion occurs. In support of this model, we show that the threshold temperature for paralysis is reduced in shi(ts) fli es when CNS activity is increased by pharmacological or genetic manipu lations, and that subanesthetic concentrations of CO2 aggravate, rathe r than alleviate, the t.s. paralytic phenotype of hypoactive para(ts) flies defective in axonal voltage-gated sodium channels.